Saturday, April 22, 2006

The evolution of clots #5

The evolution of clots, Daily Telegraph, April 4, 2006 ... Intelligent Design is the logic of ignorance - complex life, such as the machinery of blood clotting, can be explained by Darwinism, says Steve Jones ... Continued from part #4.

[Graphic: "Thrombus Formation I - Platelet Activation," Internet Stroke Center.]

Again, keep in mind what genetics professor Steve Jones (my namesake) claimed, that "the machinery of blood clotting, can be explained by Darwinism," that is the natural selection of random micromutations (NSRM).

To give a feel for the complexity of the blood clotting cascade, and therefore the difficulty facing a `blind watchmaker' in constructing it, step-by-tiny-step, here are quotes from my biology and molecular textbooks:

"Blood Clotting Blood must be a free-flowing liquid if it is to circulate easily through blood vessels, but this liquidity can also cause serious problems. Any injury that breaks a large blood vessel can quickly lead to a serious loss of blood. This is countered by a complex clotting (coagulation) mechanism. Clots form temporary barriers to blood loss until a vessel's walls have healed. When a blood vessel is injured, blood platelets begin to congregate near the cut or injury, forming a barrier known as the platelet plug. There are 200 to 400 platelets per mm3 of blood. Platelets are fragments of large bone marrow cells, called megakaryocytes, that disintegrate and discharge them into the bloodstream. When platelets come into contact with an injured vascular wall, they swell up, become sticky, and release certain, chemicals. Some of these chemicals stimulate the blood vessel to constrict; some increase the tendency of platelets to form a plug; and some help initiate the process of blood clotting. Blood clotting requires a complex and precise series of reactions that satisfy the requirement for a delicate balance between quick and efficient clot formation as a response to significant blood vessel damage and prevention of accidental formation of clots that interfere with normal circulation. Since blood clotting is so complex, we will consider only the major events involved ... Prothrombin and fibrinogen are two proteins manufactured by the liver that are always present in the plasma. Injured tissues and platelets release prothrombin activator and this along with calcium ions (Ca++) convert prothrombin into the enzyme thrombin. Thrombin in turn, acts as an enzyme that severs two short amino acid chains from each fibrinogen molecule. These activated fragments then join end to end, forming long threads of fibrin. Fibrin threads wind around the platelet plug in the damaged area of the blood vessel and provide the framework for the clot." (Mader S.S., "Biology," [1985], Wm. C. Brown Co: Dubuque IA, Third Edition, 1990, pp.524-525. Emphasis original)

I like the `Rube Goldberg' touch above, that "Platelets are fragments of large bone marrow cells, called megakaryocytes, that disintegrate and discharge them into the bloodstream"! See also below that "Platelets are formed from bits of cytoplasm that are pinched off from very large cells (megakaryocytes) in the bone marrow. Thus, a platelet is not a whole cell but a fragment of cytoplasm enclosed by a membrane."

"Platelets Function in Blood Clotting In most vertebrates other than mammals, the blood contains small, oval cells called thrombocytes, which have nuclei. In mammals thrombocytes are tiny spherical or disc-shaped bits of cytoplasm that lack a nucleus. They are usually referred to as blood platelets. About 300,000 platelets per microliter are present in human blood. Platelets are formed from bits of cytoplasm that are pinched off from very large cells (megakaryocytes) in the bone marrow. Thus, a platelet is not a whole cell but a fragment of cytoplasm enclosed by a membrane. Platelets play an important role in hemostasis (the control of bleeding). When a blood vessel is cut, it constricts, reducing loss of blood. Platelets stick to the rough, cut edges of the vessel, physically patching the break in the wall. As platelets begin to gather, they release ADP, which attracts other platelets. Within about 5 minutes after injury a complete platelet patch, or temporary clot, has formed. At the same time that the temporary clot forms, a stronger, more permanent clot begins to develop. More than 30 different chemical substances interact in this very complex process. The series of reactions that leads to clotting is triggered when one of the clotting factors in the blood is activated by contact with the injured tissue. ... Prothrombin, a plasma protein manufactured in the liver, requires vitamin K for its production. In the presence of clotting factors, calcium ions, and compounds released from platelets, prothrombin is converted to thrombin. Then thrombin catalyzes the conversion of the soluble plasma protein fibrinogen to an insoluble protein, fibrin. Once formed, fibrin polymerizes, producing long threads that stick to the damaged surface of the blood vessel and form the webbing of the clot. These threads trap blood cells and platelets, which help to strengthen the clot." (Solomon E.P., Berg L.R., Martin D.W. & Villee C.A., "Biology," [1985], Harcourt Brace: Orlando FL, Third Edition, 1993, pp.885-886. Emphasis original).

Note: More than 30 different chemical substances interact in this very complex process (my emphasis)!

"HOW DOES BLOOD CLOT? The hypotheses suggested by the various experiments outlined here have been corroborated: both damaged tissues and disintegrating platelets release a complex substance, called thromboplastin, that initiates blood clotting. For reasons not well understood, however, thromboplastin is not effective unless calcium ions are present. ... Two substances essential for normal blood clotting, then, are thromboplastin and calcium ions; a third is the plasma protein fibrinogen. But if we mix these three substances in a dish, no clotting occurs. Clearly, something else must be involved. That something else seems to be one of the globulin proteins of the plasma, known as prothrombin. If prothrombin is added to the mixture of fibrinogen, thromboplastin, and calcium ions, a clot will form. It can be demonstrated, however, that prothrombin itself has no effect on clotting; it must first be converted into thrombin, the substance that converts fibrinogen into its crystalized form, fibrin, of which the clot is made. Now we have identified the main ingredients in the clotting process. Thromboplastin, produced by disintegrating platelets or damaged tissue, converts the plasma protein prothrombin into thrombin; this is the reaction in which the calcium ions participate. The thrombin then converts another plasma protein, fibrinogen, into fibrin. The fibrin fibers form a meshwork, which begins to shrink; finally, the fluid blood serum is squeezed out, and a hardened clot is left in place. ... Actually, numerous other substances-accelerators, inhibitors, and the like-also play roles in the clotting process. A reaction series of this sort in which the first step releases another, which then triggers yet another, and so on, is referred to as a cascade reaction." (Keeton W.T., Gould J.L. & Gould C.G., "Biological Science," [1967], W.W. Norton & Co: New York NY, Fourth Edition, 1986, p.343. Emphasis original)

This is also a neat touch, that prothrombin is inactive but ready to be converted to its active form, thrombin, which then converts the inactive fibrogen into the active fibrin! Isn't the `blind watchmaker' so clever and so far-sighted! ;-)

"Blood clotting When blood is exposed to air, even in a test tube, it forms a clot, thrombus, within a few minutes. The yellowish fluid outside the clot is serum, which is plasma minus some of the protein constituents that help form the clot. The reactions leading to clot formation are extremely complex. They involve a cascade of perhaps 12 sequential enzymatic reactions, with 'failsafe thresholds' at each stage to prevent accidental triggering of clot formation. Each reaction converts an inactive form of an enzyme into an active form, which is capable of catalysing the next reaction of the cascade and producing hundreds of active products. Thus, the number of products is multiplied at each step. The final reaction involves the enzyme thrombin, which converts soluble plasma protein, fibrinogen, into fine strands of insoluble fibrin. These fibres form a meshwork that traps erythrocytes and platelets to form a clot ... When a vessel is broken, the endothelial layer is breached, exposing collagen fibres in the deeper layers. Platelets immediately attach to the collagen and each other. Thrombin, which forms as outlined above, has three effects on platelets. It causes them to: * become sticky and attach to fibrinogen; * become fragile and release ADP, which enhances linking with fibrinogen; * form long pseudopod-like processes, which attach to adjacent platelets. Thrombin converts fibrinogen to fibrin, which further strengthens the clot. The gap in the vessel quickly fills with a mat of fibrin and aggregated platelets. Thrombin apparently stimulates platelets to contract, squeezing serum from the clot and drawing the broken edges of the vessel together. Platelets also release a substance that makes the surrounding blood vessels contract, further reducing the blood flow to the area. " (Knox B., Ladiges P. & Evans B., eds., "Biology," [1994], McGraw-Hill: Sydney, Australia, 1995, reprint, pp.466-467. Emphasis original).

Note: The reactions leading to clot formation are extremely complex. They involve a cascade of perhaps 12 sequential enzymatic reactions, with 'failsafe thresholds' at each stage to prevent accidental triggering of clot formation! Maybe it wasn't a `blind watchmaker' who designed this after all? ;-) Keep this in mind when in the next part we see Jones in the next part #6 dismissing this as, "the rickety apparatus that stops us from bleeding was assembled from random bits that just happened to be hanging around."

"How does blood clot? Step 1 A blood clot is initiated by the binding of a membrane receptor by a circulating protein factor. Step 2 The complex of protein receptor and protein factor then binds with factor 10, changing it to the active form, factor 10a. Step 3 Each molecule of 10a binds to another protein factor, and this complex catalyzes the conversion of prothrombin to thrombin. Step 4 Thrombin interacts with fibrinogen, promoting its conversion to fibrin. Finally fibrin traps blood cells that seal the wound. ... Platelets Help Blood to Clot. Certain large cells within the bone marrow, called megakaryocytes, regularly pinch off bits of their cytoplasm. These cell fragments, called platelets, contain no nuclei; they enter the bloodstream, where they play an important role in controlling blood clotting. A blood clot is a seal of a ruptured blood vessel. The ruptured vessel seals itself by generating a matrix of long fibers and trapped cells that fills the gap from components present in the plasma. In a clot the gluey substance is a protein called fibrin (derived from fibrinogen), which sticks platelets together to form a tight, strong seal. Recently scientists have discovered that the fibrin that forms blood clots is generated in a spreading cascade of molecular events ... The clotting process is initiated by injury to blood vessel cells attracting platelets, which releases a protein factor that starts the cascade. At each stage in the cascade that follows, proteins from cells and blood combine in fast-rising waves, involving many more molecules in the progressive steps of the process. Billions of molecules of fibrin can be formed from a single clot-initiating event." (Raven P.H. & Johnson G.B., "Biology," [1986], Wm. C. Brown: Dubuque IA, Third Edition, 1995, p.1064. Emphasis original)

Note: "At each stage in the cascade that follows, proteins from cells and blood combine in fast-rising waves, involving many more molecules in the progressive steps of the process. Also keep this amplification function of the cascade when in the next part #6 consider Jones' dismissal of this as "the rickety apparatus that stops us from bleeding ..."

"Blood Clotting We all get cuts and scrapes from time to time, yet we do not bleed to death because blood contains a self-sealing material that plugs leaks in our vessels. The sealant is always present in our blood in an inactive form called fibrinogen. A clot forms only when this plasma protein is converted to its active form, fibrin, which aggregates into threads that form the fabric at the clot. The clotting mechanism usually begins with the release of clotting factors from platelets and involves a complex chain of reactions that ultimately transforms fibrinogen to fibrin .... More than a dozen clotting factors, have been discovered, and the mechanism is still not fully understood. ... The clotting process begins when the endothelium of a vessel is damaged and connective tissue in the vessel wall is exposed to blood. Platelets adhere to collagen fibers in the connective tissue and release a substance that makes nearby platelets sticky. (2) The platelets form a plug that provides emergency protection against blood loss. (3) This seal is reinforced by a clot of fibrin when vessel damage is more severe. Fibrin is formed via a multistep process: Clotting factors released from the clumped platelets or damaged cells mix with clotting factors in the plasma, forming an activator that converts a plasma protein called prothrombin to its active form, thrombin. Calcium and vitamin K are among the plasma factors required for this step. Thrombin itself is an enzyme that catalyzes the final step of the clotting process, the conversion of fibrinogen to fibrin. Thus, in a cascade of reactions, injury activates prothrombin to thrombin, which then activates fibrinogen to fibrin. The threads of fibrin become interwoven into a patch." (Campbell N.A., Reece J.B. & Mitchell L.G., "Biology," [1987], Benjamin/Cummings: Menlo Park CA, Fifth Edition, 1999, pp.824-825. Emphasis original)

Note: "The clotting mechanism involves a complex chain of reactions .... More than a dozen clotting factors, have been discovered, and the mechanism is still not fully understood"!

Finally, here are two quotes from one of my molecular biology textbooks:

"An example of how prostaglandins function in paracrine signaling is seen in the activation of blood platelets. Platelets are essential components of the blood-clotting mechanism that plug sites where blood vessels are ruptured. Platelets are not true cells; they have no nucleus, and are produced by the fragmentation of certain bone marrow cells. Clotting is a complex cascade of enzymatic events that is triggered by injury and leads rapidly to the formation of a clot, a tangled mass of red blood cells, platelets, and fibers of a protein called fibrin. The clotting mechanism must be carefully regulated, because inappropriate blood clots lead quickly to life-threatening situations. The coronary arteries of the heart are only 1 millimeter or so in diameter, and most heart attacks result from a small blood clot that blocks coronary circulation. Similarly, clots in the venous system can produce phlebitis (inflammation of the veins) in the lower limbs and embolisms (obstructions) in the lungs. Thus, clot formation is essential, but it must be confined to the area where the damage occurs. Platelets have many different receptors that sense when a tissue is damaged. Most relevant to our discussion of paracrine regulation, platelets can be activated by members of the prostaglandin family such as thromboxane A2, as well as by extracellular adenosine diphosphate. These substances are released by activated platelets and then function as paracrine hormones to activate other platelets. ... Most of the known platelet activators act through G protein-linked receptors to activate phospholipase C, which triggers the release of calcium from a calcium-storing tubular network known as the dense tubular system; this results in the release of arachidonic acid. An enzymatic pathway starting with cyclooxygenase then converts the arachidonic acid to thromboxane A2. Thromboxane A2 diffuses out of the platelet and acts on G protein-linked thromboxane receptors of neighboring platelets. The thromboxane receptors in turn activate phospholipase C, triggering the activation of nearby platelets. As a result, platelets in the area are recruited to the site of injury." (Becker W.M., Kleinsmith L.J. & Hardin J., "The World of the Cell," [1986], Benjamin/Cummings: San Francisco CA, Fourth edition, 2000, p.294. Emphasis original)

See above and previous (here and here) about the `Rube Goldberg' touch! See also an excerpt from Behe's "Darwin's Black Box" section, "Rube Goldberg In The Blood."

"The Process of Platelet Activation. (a) Platelets are activated by several substances and aggregate upon activation, forming a blood clot. (1) Collagen exposed in a damaged blood vessel wall stimulates platelet activation and adherence. (2) Activated platelets release the platelet factors ADP and thromboxane A2 (TA2), which (3) stimulate the activation and aggregation of more platelets -the vicinity. The release of A2 and ADP is an example of paracrine signaling. (b) Paracrine signaling by platelets uses some of the same classes of receptors and signal transduction pathways described for the endocrine hormones. The receptors for thrombin, TA2, and collagen all appear to be G protein-linked receptors that activate phospholipase C. However, the activation of the thrombin receptor is unusual in that it depends on the protease thrombin removing a portion of the receptor protein. When newly exposed collagen in a damaged blood vessel wall binds to a G protein-linked collagen receptor, membrane phospholipase C is activated, causing the production of InsP3 and DAG, and ultimately the release of calcium from the dense tubular system. Increased calcium concentration inside the platelet stimulates the secretion of granules that contain growth factors and ADP. Phospholipase A is thought to be simultaneously activated by a G protein. The activation of phospholipase A2 releases arachidonic acid, which is converted to TA2. TA2 binds to the TA2 receptors on nearby platelets, causing elevated calcium levels, whereas ADP binds to what is probably a ligand-gated calcium channel. Both messengers stimulate platelets to aggregate." (Becker, Ibid., 2000, p.295)

There is also a nice graphic demonstration of blood clotting at McGraw-Hill's "Essential Study Partner" site.

To try to even imagine this being put together, step-by-tiny-step, by a `blind watchmaker', who is nothing but "the blind forces of physics," "Natural selection, the blind, unconscious, automatic process," which "has no purpose in mind. It has no mind and no mind's eye. It does not plan for the future. It has no vision, no foresight, no sight at all":

"All appearances to the contrary, the only watchmaker in nature is the blind forces of physics, albeit deployed in a very special way. A true watchmaker has foresight: he designs his cogs and springs, and plans their interconnections, with a future purpose in his mind's eye. Natural selection, the blind, unconscious, automatic process which Darwin discovered, and which we now know is the explanation for the existence and apparently purposeful form of all life, has no purpose in mind. It has no mind and no mind's eye. It does not plan for the future. It has no vision, no foresight, no sight at all. If it can be said to play the role of watchmaker in nature, it is the blind watchmaker."(Dawkins R., "The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe Without Design," W.W Norton & Co: New York NY, 1986, p.5)

It just occurred to me (although I have a vague idea I said before), that if the Darwinists really thought that "the machinery of blood clotting, can be explained by Darwinism" then why 1) : did they never mention it until Behe brought it up? and; 2) do they waste their time on comparatively trivial examples like peppered moths and finch beaks?

[Continued in part #6]

Stephen E. Jones, BSc (Biol).
"Problems of Evolution"

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